Enhanced antibody-dependent cellular cytotoxicity in HIV vaccine by novel adjuvant

The National Institute of Allergy and Infectious Diseases (NIAID) awarded The Ohio State University a Project Grant totaling $433,125 under the Allergy and Infectious Diseases Research program (CFDA 93.855) on August 21, 2025, with performance completion targeted for July 31, 2027. This exploratory research initiative addresses HIV vaccine development by investigating the use of a novel oral adjuvant to enhance antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Building upon the RV144 vaccine regimen, the research will examine phenotypic, functional, and molecular changes in NK cell subsets across various tissues in nonhuman primate models following RV144-like vaccination with the adjuvant candidate.

The primary deliverable is an evaluation of the novel adjuvant's capacity to strengthen NK cell activity and antiviral effects against SIV/HIV, with anticipated results informing the advancement of preventive HIV vaccines and therapeutic interventions. Research activities include translational studies examining enhanced ADCC capability of NK cells, with particular focus on KLRG1+ NK cell expansion, which preliminary murine model studies indicated produces promising results. The knowledge generated through this project is intended to contribute to the broader scientific understanding of NK cell-mediated immunity and support the development of more effective HIV prevention strategies.

Abstract

This exploratory study addresses the challenge of developing an effective HIV vaccine by focusing on natural killer (NK) cells and their ability to mediate antibody-dependent cell-mediated cytotoxicity (adcc). Building on the RV144 vaccine regimen, which demonstrated some efficacy in preventing HIV infection, the study explores using a novel oral adjuvant to enhance NK cell cytotoxicity and adcc activity in the nonhuman primate model. Preliminary studies in a murine model showed promising results with this adjuvant, leading to the expansion of KLRG1+ NK cells known for their adcc capacity. The study aims to investigate phenotypic, functional, and molecular changes in NK cell subsets in various tissues following RV144-like vaccination with the novel adjuvant. Additionally, the research aims to assess the enhanced antiviral effects and increased adcc capability of NK cells induced by the combined vaccine and novel adjuvant. This innovative approach seeks to discover a novel vaccine adjuvant that strengthens NK cell activity against SIV/HIV in different tissues, potentially advancing the development of preventive HIV vaccines and therapeutic interventions.